Cystic fibrosis (CF) remains a leading cause of childhood respiratory morbidity and premature mortality. The condition is a result of mutations in the gene that codes for an epithelial transmembrane chloride channel, called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Currently there is no cure for cystic fibrosis. The only treatment option that attempts to restore normal lung function to CF patients is lung transplantation. An alternative approach to a future cure could be the delivery of a cell-based therapy, involving the delivery of cells with functional CFTR that might integrate into the respiratory tract.
Scientists at The Ritchie Centre are investigating the ability of fetal and adult stem cells, including human amnion epithelial cells (hAECs) and induced pluripotent stem cells (iPSCs), to differentiate into lung epithelial cells in vitro, to express functional CFTR and to engraft in the respiratory airway. They have employed novel research tools, including the Australian Synchrotron and the Advanced Light Source in Berkley, California, to demonstrate that hAECs can be manipulated to express the CFTR gene and form 3-dimensional structures that expressed the CFTR protein in a polarized manner, similar to that observed in normal lung epithelial tissue.
In addition, they have demonstrated that the ion channels within the CFRT are functional and able to secrete chloride ions from within the cell. In collaboration with colleagues at RMIT, they are now investigating the application of novel “Surface Acoustic Wave” nebulization technologies to facilitate administration and engraftment of these cells into the respiratory tract. This research, which has been supported by a grant from the Australian Cystic Fibrosis Research Trust, suggests that hAECs may provide a platform for the development of a cellular therapy for cystic fibrosis.